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Showing papers in "Ejso in 2018"


Journal ArticleDOI
01 May 2018-Ejso
TL;DR: It is suggested that the preoperative NLR is an additional useful predictor of both long-term and short-term outcomes in gastric cancer patients.
Abstract: Background The preoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic marker for gastric cancer patients. However, the utility of the NLR in predicting short-term outcomes in gastric cancer patients remains unclear. Here, we investigated whether the preoperative NLR is a predictor of short-term outcomes in gastric cancer patients. Methods We retrospectively evaluated 154 consecutive gastric cancer patients. We compared the perioperative outcomes and median survival times (MSTs). In particular, for stage II/III (UICC, 7th edition) gastric cancer patients, we compared median disease-free survival time (MDFST) between the low- and high-NLR groups. Results Between the low-NLR group (n = 110) and the high-NLR group (n = 44), significant differences were observed in perioperative outcomes, including postoperative complications (3 (2.7%) vs. 5 (11.3%); p = 0.015), intraoperative blood loss (158 ± 168 g vs. 232 ± 433 g; p = 0.022), and intraoperative blood transfusions (0 vs. 3 (6.8%); p = 0.042). MSTs and MDFSTs were also significantly different (812 vs. 594 days, p = 0.04; and 848 vs. 475 days, p = 0.03, respectively). Multivariate analysis identified the NLR (hazard ratio [HR], 2.015; p = 0.004), Glasgow Prognostic Score (GPS) (HR, 1.533; p = 0.012), and presence of stage III/IV disease (HR, 5.488; p Conclusions We suggest that the preoperative NLR is an additional useful predictor of both long-term and short-term outcomes in gastric cancer patients.

141 citations


Journal ArticleDOI
01 May 2018-Ejso
TL;DR: Comprehensive management of patients with operable and advanced cancer should integrate the host systemic inflammatory response by calculating the 3 scale modified Glasgow prognostic score, and there is no sufficient evidence to support their use in clinical practice.
Abstract: Chronic inflammation is an aberrantly prolonged form of a protective response to a loss of tissue homeostasis and it is involved in several steps of the carcinogenesis process. As a result, many cancers are inflammation-related. The systemic inflammatory response is associated with survival in advanced and localized cancers. Two categories of scores have been proposed to monitor the systemic inflammatory response, those derived from protein measurement and those based on counting inflammatory cells. This review aims to provide a critical appraisal of these 2 categories of surrogate markers. The 3 scale modified Glasgow prognostic score (mGPS) is based on the combination of C-reactive protein and albumin and is graded 0 to 2. It has been validated worldwide showing an independent prognostic value in patients with cancer in a variety of tumour types and tumour stages. Leukocytes-based scores are mainly neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR). Elevated NLR and/or PLR and lower LMR seem to be associated with decreased survival, but the studies about these markers are very heterogeneous. The main limit is the variety of thresholds used to dichotomize patients, so that reproducibility and reliability of leukocytes-based scores can be questioned. Hence, there is no sufficient evidence to support their use in clinical practice. Comprehensive management of patients with operable and advanced cancer should integrate the host systemic inflammatory response by calculating the mGPS. It could be a helpful tool to tailor patients' management.

116 citations


Journal ArticleDOI
01 Nov 2018-Ejso
TL;DR: Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes, and properly selected patients should be considered for surgical resection.
Abstract: With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age. The heterogeneity of this group, combined with the limited available data, impedes drafting evidence-based guidelines. Therefore, a multidisciplinary task force convened experts from the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology and the American College Surgeons Commission on Cancer, with the goal of identifying the best practice to promote personalized rectal cancer care in older patients. A crucial element for personalized care was recognized as the routine screening for frailty and geriatrician involvement and personalized care for frail patients. Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes. Therefore, properly selected patients should be considered for surgical resection. Local excision can be utilized when balancing oncologic outcomes, frailty and life expectancy. Watch and wait protocols, in expert hands, are valuable for selected patients and adjuncts can be added to improve complete response rates. Functional recovery and patient-reported outcomes are as important as oncologic-specific outcomes in this age group. The above recommendations and others were made based on the best-available evidence to guide the personalized treatment of elderly patients with rectal cancer.

110 citations


Journal ArticleDOI
30 Apr 2018-Ejso
TL;DR: Given the growing body of evidence on prehabilitation efficacy, this narrative review will summarize the rational underlying preoperative interventions, and propose a structured clinical pathway aimed at optimizing preoperative functional capacity.
Abstract: Cancer and its treatments are associated with functional decline that has impactful consequences on quality of life, and care continuum. Thus, optimizing perioperative functional capacity has been identified as a research and clinical priority in cancer care. The process of enhancing physical fitness before an operation to enable the patient to withstand the stress of surgery has been termed prehabilitation. Main elements are preoperative exercise, nutrition therapy, and anxiety-reduction techniques. Given the growing body of evidence on prehabilitation efficacy, this narrative review will summarize the rational underlying preoperative interventions, and propose a structured clinical pathway aimed at optimizing preoperative functional capacity.

90 citations


Journal ArticleDOI
01 Dec 2018-Ejso
TL;DR: This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients, emphasising the necessity to reach consensus on several issues of this comprehensive procedure.
Abstract: Background At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice. Methods HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and countrywide practice. Results It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies. Conclusion This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed.

89 citations


Journal ArticleDOI
01 Apr 2018-Ejso
TL;DR: Mesorectal excision with lateral lymph node dissection is not associated with a significant increase in the incidence of urinary dysfunction, andUrinary dysfunction is associated with tumor location and blood loss.
Abstract: Background Postoperative urinary dysfunction is a major complication of rectal cancer surgery. A randomized controlled trial (JCOG0212) concluded that the noninferiority of mesorectal excision alone to mesorectal excision with lateral lymph node dissection was not confirmed in terms of relapse-free survival. Methods Eligibility criteria included histologically proven clinical stage II/III rectal cancer, a main lesion located in the rectum with the lower margin below the peritoneal reflection, and the absence of lateral lymph node enlargement. After confirming R0 resection by mesorectal excision, patients were randomized intraoperatively. The residual urine volume was measured three times. Urinary dysfunction was defined as ≥50 mL residual urine occurring at least once or no measurement of residual urinary volume. This trial was registered with the UMIN Clinical Trials Registry, number C000000034. Results In the mesorectal excision alone and the mesorectal excision with lateral lymph node dissection groups, the incidence of early urinary dysfunction were 58% and 59%, respectively. A tumor location in the lower rectum (vs. upper rectum) and a blood loss of ≥500 mL (vs. Conclusions Mesorectal excision with lateral lymph node dissection is not associated with a significant increase in the incidence of urinary dysfunction. Urinary dysfunction is associated with tumor location and blood loss.

87 citations


Journal ArticleDOI
01 Jul 2018-Ejso
TL;DR: AR seemed to offer an advantage versus NAR in terms of DFS and OS among patients undergoing resection of HCC - especially among patients without cirrhosis, and should be considered the preferred surgical option for patients with HCC when feasible.
Abstract: Objective The relative benefit of anatomic resection (AR) versus non-anatomic resection (NAR) of HCC remains poorly defined. We sought to evaluate the available evidence on oncologic outcomes, as well as the clinical efficacy and safety of AR versus NAR performed as the primary treatment for HCC patients. Material and methods A systematic review and meta-analysis was conducted using Medline, ClinicalTrials.gov and Cochrane library through April 15th, 2017. Only clinical studies comparing AR versus NAR were deemed eligible. Results A total of 43 studies were considered eligible (total 12,429 patients: AR, n = 6839 (55%) versus NAR, n = 5590 (45%)). Blood loss was higher among patients undergoing AR (mean difference: +229.74 ml, 95% CI: 97.09–362.38, p = 0.0007), whereas resection margin was slightly wider following AR versus NAR (mean difference: +0.29 cm, 95% CI: 0.15–0.44, p Conclusion Despite the high heterogeneity among studies, the data demonstrated that AR had comparable perioperative morbidity and mortality versus NAR. AR seemed to offer an advantage versus NAR in terms of DFS and OS among patients undergoing resection of HCC – especially among patients without cirrhosis. Thus, AR should be considered the preferred surgical option for patients with HCC when feasible.

82 citations


Journal ArticleDOI
01 Oct 2018-Ejso
TL;DR: Breast cancer is present in transgender men and the risk is dependent on top surgery; those with top surgery appear to be lower risk than natal females; more longitudinal studies and better population data are required to contribute to evidence-based screening recommendations.
Abstract: Transgender men or Female-to-Male (FtM) patients' risk of breast cancer and screening recommendations remain unclear. The objective of this study is to perform a systematic review of the literature and document all reported cases of FtM breast cancer as well as provide research recommendations. Following PRISMA guidelines, MEDLINE, ProQuest, PubMed, and Cochrane Database of Systematic Reviews were searched from inception until September 15, 2016. Screening and data extraction were performed in duplicate by two independent reviewers (RH and JS). Study quality was assessed using a component-based system. Study characteristics, patient demographics, breast cancer characteristics, presentation and management are reported. Eight articles met inclusion criteria representing 17 transgender men with breast cancer. Median age at diagnosis was 44.5 years. Breast cancer types included: 8 invasive ductal carcinomas, two tubular carcinomas and seven unrecorded. Twelve of the 14 known hormone status tumours were estrogen receptor positive (85.7%), of which nine were also progesterone positive. The most common was breast lump (n = 6) and four patients had local regional or distant disease at presentation. Management was reported for ten patients: six patients underwent mastectomy (60.0%), three radiation (30.0%), and five chemotherapy (50.0%). Breast cancer is present in transgender men and the risk is dependent on top surgery; those with top surgery appear to be lower risk than natal females. More longitudinal studies and better population data are required to contribute to evidence-based screening recommendations.

82 citations


Journal ArticleDOI
01 Sep 2018-Ejso
TL;DR: Ulasound-guided wire localization of the target lymph node is not suitable for clinical practice because of limitations regarding clip visibility and selective surgical preparation of thetarget lymph node.
Abstract: Introduction Clipping and selective removal of initially suspicious axillary lymph nodes in breast cancer patients who have been sonographically down-staged by primary systemic therapy improves the accuracy of surgical staging and provides the opportunity for more conservative axillary surgery. This study evaluated whether preoperative ultrasound-guided wire localization of the clipped node is useful for routine clinical practice. Material and methods This prospective, single-center feasibility trial included patients with invasive breast cancer (cT1-3N1-3M0) treated by primary systemic therapy. They underwent ultrasound-guided core needle biopsy and clip placement into the most suspicious axillary lymph node prior to chemotherapy. After primary systemic therapy the clipped lymph node was localized by a wire. All patients underwent target lymph node biopsy, completion axillary lymph node dissection and, if yiN0, axillary sentinel lymph node biopsy. The primary study endpoint was the identification rate of the target lymph node. Results All patients (n = 30) underwent successful clip insertion into the lymph node. After chemotherapy, the clipped target lymph node was visible by ultrasound in 83.3% (25/30). Wire localization was possible in 24 cases (80%), and the clipped node identification rate was 70.8% (17/24 cases). In 9/30 patients (30%) clipped node removal was not confirmed by intraoperative radiography. Conclusion Ultrasound-guided wire localization of the target lymph node is not suitable for clinical practice because of limitations regarding clip visibility and selective surgical preparation of the target lymph node. Further prospective evaluation of alternative techniques is needed.

78 citations


Journal ArticleDOI
01 Oct 2018-Ejso
TL;DR: Whereas neoadjuvant FOLFIRINOX rarely achieves resectability in patients with LAPC, most BRPC undergo resection, and three patients with complete pathological response are disease-free after mean follow-up of 19 months, there is a trend towards improved survival compared with patients undergoing up-front surgery.
Abstract: Objective To assess clinical and pathologic efficacy of neoadjuvant FOLFIRINOX for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). Methods Patients receiving neoadjuvant FOLFIRINOX for LAPC and BRPC treated between 2014 and 2017 were identified. Post-treatment patients achieving resectability were referred for surgery, whereas unresectable patients continued chemotherapy. Clinical and pathological data were retrospectively compared with control group consisting of 47 consecutive patients with BRPC undergoing pancreatic and portal vein resection between 2008 and 2017. Results Thirty LAPC and 23 BRPC patients were identified. Reasons for unresectability included disease progression (70%), locally unresectable disease (18%), and poor performance status (11%). Three patients (10%) with LAPC, and 20 (87%) with BRPC underwent curative surgery. Compared with control group, perioperative complication rate (4.3% versus 28.9%, p = 0.016), and pancreatic fistula rate (0 versus 14.8%, p = 0.08) were lower. Peripancreatic fat invasion (52.2% vs 97.8%, p = 0.001), lymph node involvement (22% vs 54.3%, p = 0.01), and surgical margin involvement (0 vs 17.4%, p = 0.04) were higher in the control group. Median survival was 34.3 months in BRPC patients operated after FOLFIRINOX and 26.1 months in the control group (p = 0.07). Three patients (13%) with complete pathological response are disease-free after mean follow-up of 19 months. Conclusions Whereas neoadjuvant FOLFIRINOX rarely achieves resectability in patients with LAPC (10%), most BRPC undergo resection (87%). Neoadjuvant FOLFIRINOX leads to complete pathological response in 13% of cases, tumor downstaging, and a trend towards improved survival compared with patients undergoing up-front surgery.

75 citations


Journal ArticleDOI
01 Jul 2018-Ejso
TL;DR: Standardization of the procedure will facilitate future international multicenter prospective clinical trials and confirm that PIPAC procedures are homogeneously performed in established centers.
Abstract: Background Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method offered in selected patients suffering from non-resectable peritoneal carcinomatosis (PC). As reported experience is still limited, we conducted a survey among active PIPAC centers aiming to report their technical approach and clinical findings. Methods An online survey was sent to active PIPAC centers worldwide. The questionnaire consisted of 34 closed questions and was conducted over a period of 3 months beginning in March 2017. Results Nine out of 15 contacted centers completed the questionnaire totaling 832 PIPAC procedures in 349 patients. Most common indications for PIPAC were PC from gastric, ovarian and colorectal origin. The mean time between each PIPAC procedure was 6–8 weeks. Seven of nine (77.8%) centers evaluate the PCI at every PIPAC procedure. At least four tissue samples for histopathology analysis were retrieved in 5 (55.6%). All centers (100%) use the same chemotherapy protocol: oxaliplatin at a dosage of 92mg/m2 for PC of colorectal origin and a combination of cisplatin and doxorubicin at a dosage of 7.5mg/m2 and 1.5mg/m2, respectively, for other types of PC. Eight centers (88.9%) perform routine radiological evaluation before first PIPAC and after third PIPAC. Conclusion These data confirm that PIPAC procedures are homogeneously performed in established centers. Standardization of the procedure will facilitate future international multicenter prospective clinical trials.

Journal ArticleDOI
01 Jan 2018-Ejso
TL;DR: Although M1 disease portends poor prognosis regardless of LN status, LNM predicts worse OS in a histology-dependent manner in M0 disease.
Abstract: Introduction The incidence and clinical significance of lymph node metastasis (LNM, N1) in soft tissue sarcoma (STS) is unclear. Recent studies have focused on extremity/trunk STS (ETSTS). We sought to define the subgroup of patients with LNM at sarcoma diagnosis across all disease sites and histologies. Methods We identified and categorized 89,870 STS patients from the National Cancer Data Base (1998–2012) by nodal stage. Pathologically confirmed LNM (pN1) were identified in 1404 patients; 1750 had clinically suspicious but not pathologically confirmed LNM (cN1). Survival analyses were performed by Kaplan-Meier method. Results Of 3154 patients (3.5%) with pN1 or cN1 LNM at presentation, 1310 had synchronous distant metastasis (M1). LNM affected a small proportion of patients (5.8% head/neck, 5.3% intrathoracic, 5.1% intra-abdominal, 2.0% ETSTS). Angiosarcoma (6%), epithelioid (13%), clear cell (16%), and small cell sarcoma (19%) had the highest incidence of LNM, although liposarcoma, fibrous histiocytoma, and leiomyosarcoma accounted for the greatest number of LNM patients. For pN1M0 disease, median overall survival (OS) was 28.2 months, varying by histology. Among patients with pN1M0 STS, angiosarcoma, clear cell sarcoma, leiomyosarcoma, and fibrous histiocytoma were associated with worse median OS (19.4, 23.8, 27.1, and 29.3 months) compared to epithelioid sarcoma and liposarcoma (49.6 and 56.0 months, p Conclusion Despite clinical suspicion, pathologic LN evaluation in STS is inconsistently performed. LNM occurs across anatomic disease sites and is unevenly distributed across histologies. Although M1 disease portends poor prognosis regardless of LN status, LNM predicts worse OS in a histology-dependent manner in M0 disease.

Journal ArticleDOI
01 Oct 2018-Ejso
TL;DR: Both of pretreatment plasma D-dimer and fibrinogen were robust predictors of poor survival in digestive cancer patients with different traits, and further studies are warranted to verify their roles on cancer prognosis.
Abstract: Background Abnormalities of coagulation and fibrinolysis are frequently observed in cancer patients. Emerging data suggested that plasma D-dimer and fibrinogen levels correlated with tumor stage and prognosis in several cancer types. The aim of this study is to systematically review the prognostic value of plasma D-dimer and fibrinogen in digestive cancers. Materials and methods We searched major database for manuscripts reporting the effect of pretreatment plasma d-dimer or fibrinogen on survival of digestive cancer patients. Revman5.3 and R were the software used for analysis. Pooled multivariable-adjusted hazard ratios (HR) for overall survival (OS) were calculated in all patients and many different subgroup analyses by stratifying on metastasis stage, tumor type, ethnicity, cutoff points and average age. Results 37 original studies were included for analysis. Increased levels of plasma D-dimer showed stronger association with worse OS than fibrinogen in digestive cancer (HR = 2.06, 95% CI 1.79–2.38; HR = 1.60, 95% CI 1.44–1.79). The highest adverse impacts of elevated plasma D-dimer and fibrinogen on OS were revealed in colorectal cancer (HR = 2.32, 95% CI 1.89–2.85; HR = 2.20, 95% CI 1.24–3.90). The negative prognostic effects of high plasma D-dimer enhanced in metastatic patients when compared with non-metastatic digestive cancer patients, while high plasma D-dimer was more predictive non-metastatic patients. Conclusions Both of pretreatment plasma D-dimer and fibrinogen were robust predictors of poor survival in digestive cancer patients with different traits. Further studies are warranted to verify their roles on cancer prognosis.

Journal ArticleDOI
21 Mar 2018-Ejso
TL;DR: In this article, the authors evaluated Patient Reported Outcome Measurements (PROMs) scores as well as satisfaction with and expectations of the use of PROMs in breast cancer patients using the national and local patient advocate society.
Abstract: Introduction In the International Consortium for Health Outcome Measures (ICHOM) breast cancer outcome set Patient Reported Outcome Measurements (PROMs) form an important but rather innovative part. Few data exist on scores per type of breast surgery and how to use scores in surgical practice. We evaluated PROM scores as well as satisfaction with and expectations of the use of PROMs in breast cancer patients using the national and local patient advocate society. Methods Through an online survey patients were asked to report age, type of breast cancer surgery (whether Breast Conserving Therapy (BCT), mastectomy, autologous or implant breast reconstruction) and time since surgery. PROMs (EORTC-QLQ-C30/BR23 and BREAST-Q postoperative modules) were compared for the different surgeries. Additional comparison was made with literature normative and reference scores. Three questions evaluated satisfaction with PROMs and expectations. Results 496 patients completed all PROMs and 487 the satisfaction/expectation-questions. Significantly reduced physical functioning was reported following BCT as compared to other surgeries and literature reference values. Satisfaction scores were higher following autologous reconstruction and lower following implant reconstruction as compared to BCT. PRO scores were comparable to normative and references scores except for the ‘physical functioning’ (BREAST-Q) scores that reported lower in the present study. Ninety-four percent of the participants was (highly) satisfied with future PROM use. Conclusions Statistical significant differences were found for PROMs following different types of breast surgery. The significance of these results should become clearer trough collection of future data. The great majority of participants considered PROMs as (highly) acceptable and reacted positively on their proposed future use.

Journal ArticleDOI
01 Sep 2018-Ejso
TL;DR: The findings recommend putting more emphasis on preoperative management of patients at risk for surgical complications, but do not support benefit for long-term outcome.
Abstract: Background Preoperative low skeletal muscle mass and density are associated with increased postoperative morbidity in patients undergoing curative colorectal cancer (CRC) surgery. However, the long-term effects of low skeletal muscle mass and density remain uncertain. Methods Patients with stage I-III CRC undergoing surgery, enrolled in a prospective observational cohort study, were included. Skeletal muscle mass and density were measured on CT. Patients with high and low skeletal muscle mass and density were compared regarding postoperative complications, disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). Results In total, 816 patients (53.9% males, median age 70) were included; 50.4% had low skeletal muscle mass and 64.1% low density. The severe postoperative complication rate was significantly higher in patients with low versus high skeletal muscle and density (20.9% versus 13.6%, p = 0.006; 20.0% versus 11.8%, p = 0.003). Low skeletal muscle mass (OR 1.91, p = 0.018) and density (OR 1.87, p = 0.045) were independently associated with severe postoperative complications. Ninety-day mortality was higher in patients with low skeletal muscle mass and density compared with patients with high skeletal muscle mass and density (3.6% versus 1.7%, p = 0.091; 3.4% versus 1.0%, p = 0.038). No differences in DFS were observed. After adjustment for covariates such as age and comorbidity, univariate differences in OS and CSS diminished. Conclusions Low skeletal muscle mass and density are associated with short-term, but not long-term, outcome in patients undergoing CRC surgery. These findings recommend putting more emphasis on preoperative management of patients at risk for surgical complications, but do not support benefit for long-term outcome.

Journal ArticleDOI
01 Sep 2018-Ejso
TL;DR: The data suggest that neoadjuvant therapy with denosumab is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery, and confirm excellent efficacy and short-term tolerability of this drug.
Abstract: Background Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive, rarely metastazing bone tumor. This is a retrospective study evaluating a large series of GCTB patients treated with denosumab in routine practice in 6 European reference centers. Methods Patients with locally advanced, unresectable or metastatic GCTB, treated with denosumab outside clinical trials were eligible. Primary end-point was progression-free survival (PFS) for all patients; secondary end-points were: type of surgery, relapse rate and event-free survival for patients after preoperative denosumab + surgery. Results We identified 138 patients treated in the period 2011–2016. In 40/43 cases the diagnosis was confirmed by H3F3A gene mutation. Median follow-up time was 23 months (range 6–48). Primary tumor was located in lower limb (38%) - mostly in femur and tibia, in upper limb (34%), and in pelvis/axial skeleton/ribs (28%). 110 (80%) patients had primary tumors, 28 (22%) recurrent tumors after previous surgical procedures (+/− radiotherapy). 89/138 patients had locally advanced GCTB and underwent neoadjuvant denosumab. The median denosumab treatment duration was 8 months (median number of cycles 11), 98% had clinical benefit from therapy. 39 (44%) had wide en-bloc resection - WE (+implantation of the prosthesis in 17 cases), the other 50 (56%) cases had intralesional curettage - C. Progression after surgical treatment was observed in 19 patients, 16 of them after C (32%); 13 patients underwent denosumab re-challenge, and all responded. Two-year progression-free survival (PFS; from denosumab start) rate was 81%; 2-year EventFS (from surgery) was significantly better in WE group (93%) vs 55% in C group (p = 0.006). Treatment was well tolerated with only 2 cases of grade 3 toxicity and one osteonecrosis of the jaw. Conclusion Our retrospective study confirms that denosumab is extremely efficient in unresectable/metastatic disease as well as in a neoadjuvant setting. Our data confirm excellent efficacy and short-term tolerability of this drug. Our data suggest that neoadjuvant therapy with denosumab is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following denosumab raises questions about the optimal management of such cases.

Journal ArticleDOI
02 Feb 2018-Ejso
TL;DR: Electrochemotherapy of hepatocellular carcinoma proved to be a feasible and safe treatment in all 10 patients included in this study, and the results at medium observation period after treatment are encouraging.
Abstract: Background and objectives Electrochemotherapy provides non-thermal ablation of cutaneous as well as deep seated tumors. Based on positive results of the treatment of colorectal liver metastases, we conducted a prospective pilot study on hepatocellular carcinomas with the aim of testing the feasibility, safety and effectiveness of electrochemotherapy. Patients and methods Electrochemotherapy with bleomycin was performed on 17 hepatocellular carcinomas in 10 patients using a previously established protocol. The procedure was performed during open surgery and the patients were followed for median 20.5 months. Results Electrochemotherapy was feasible for all 17 lesions, and no treatment-related adverse events or major post-operative complications were observed. The median size of the treated lesions was 24 mm (range 8–41 mm), located either centrally, i.e., near the major hepatic vessels, or peripherally. The complete response rate at 3–6 months was 80% per patient and 88% per treated lesion. Conclusions Electrochemotherapy of hepatocellular carcinoma proved to be a feasible and safe treatment in all 10 patients included in this study. To evaluate the effectiveness of this method, longer observation period is needed; however the results at medium observation time of 20.5 months after treatment are encouraging, in 15 out of 17 lesions complete response was obtained. Electrochemotherapy is predominantly applicable in patients with impaired liver function due to liver cirrhosis and/or with lesions where a high-risk operation is needed to achieve curative intent, given the intra/perioperative risk for high morbidity and mortality.

Journal ArticleDOI
01 Sep 2018-Ejso
TL;DR: Surgical margins determine LR in all CS grades, but LR affects DSS only in grade-2 and grade-3 tumors, and a minimum 4-mm margin should be the aim in all cases.
Abstract: Introduction Chondrosarcoma (CS) is the second most common primary bone sarcoma with no clear role for adjuvant therapy. The purpose of this study was to investigate (1) the relationship between surgical excision margins and local recurrence free survival (LRFS), and (2) the role of local recurrence (LR) in disease specific survival (DSS) in CS of the extremity and pelvis. Material and methods 341 pelvic and extremity CS diagnosed between 2003 and 2015 were studied retrospectively. Results LR developed in 23% of cases. Pelvic location, pathologic fracture, margin and grade were significant factors for LR after univariate analysis. Multivariate analysis revealed surgical margin and pelvic location as positive factors for LR, and grade-1 and 2 CS as negative factors for LR. Pathologic fracture, central versus peripheral, grade, and LR were significant factors with univariate analysis for DSS; and grade was significant after multivariate analysis for all patients for DSS. After competing risk analysis, LR was statistically significant for DSS in grade-2 and grade-3 tumors. Conclusion Surgical margins determine LR in all CS grades, but LR affects DSS only in grade-2 and grade-3 tumors. Although narrow margins are acceptable in grade-1 tumors, since biopsy is unreliable in predicting final grade, a minimum 4-mm margin should be the aim in all cases.

Journal ArticleDOI
17 Apr 2018-Ejso
TL;DR: Accuracy of clinical lymph node staging in colorectal cancer patients is about as accurate as flipping a coin, which may lead to overtreatment of rectal cancer Patients.
Abstract: Background: This study aims to provide insight in the quality of current daily practice in clinical lymph node staging in colorectal cancer (CRC) in the Netherlands. Methods: Data of the nationwide population-based Netherlands Cancer Registry between 2003 and 2014 were used to analyze lymph node staging for cM0 CRC patients. Accuracy of clinical lymph node staging was calculated for the period 2011–2014. Analyses were performed for patients without preoperative treatment or treated with short-course radiotherapy (SCRT) followed by resection. Results: 100,211 patients were included for analysis. The proportion clinically positive lymph nodes increased significantly between 2003 and 2014 (6%–22% for colon cancer; 7%–53% for rectal cancer). The proportion histological positive lymph nodes remained stable (±35% colon, ±33% rectum). Data from 2011 to 2014 yielded a sensitivity, specificity, positive and negative predictive value of 41%, 84%, 59% and 71% for colon cancer, respectively (n = 21,629). This was 38%, 87%, 56%, 76% for rectal cancer without SCRT, (n = 2178) and 56%, 67%, 47% and 75% for rectal cancer with SCRT (n = 3401), respectively. Conclusion: Accuracy of clinical lymph node staging in colorectal cancer patients is about as accurate as flipping a coin. This may lead to overtreatment of rectal cancer patients. Acceptable specificity and NPV limit the risk of undertreatment.

Journal ArticleDOI
01 Apr 2018-Ejso
TL;DR: The European Society of Surgical Oncology (ESSO) and the European Society for Enhanced Recovery after Surgery (ERAS) as mentioned in this paper were founded with the aim of promoting nutritional assessment and perioperative nutrition with and without an enhanced recovery program.
Abstract: Malnutrition in cancer patients - in both prevalence and degree - depends primarily on tumor stage and site. Preoperative malnutrition in surgical patients is a frequent problem and is associated with prolonged hospital stay, a higher rate of postoperative complications, higher re-admission rates, and a higher incidence of postoperative death. Given the focus on the cancer and its cure, nutrition is often neglected or under-evaluated, and this despite the availability of international guidelines for nutritional care in cancer patients and the evidence that nutritional deterioration negatively affects survival. Inadequate nutritional support for cancer patients should be considered ethically unacceptable; prompt nutritional support must be guaranteed to all cancer patients, as it can have many clinical and economic advantages. Patients undergoing multimodal oncological care are at particular risk of progressive nutritional decline, and it is essential to minimize the nutritional/metabolic impact of oncological treatments and to manage each surgical episode within the context of an enhanced recovery pathway. In Europe, enhanced recovery after surgery (ERAS) and routine nutritional assessment are only partially implemented because of insufficient awareness among health professionals of nutritional problems, a lack of structured collaboration between surgeons and clinical nutrition specialists, old dogmas, and the absence of dedicated resources. Collaboration between opinion leaders dedicated to ERAS from both the European Society of Surgical Oncology (ESSO) and the ERAS Society was born with the aim of promoting nutritional assessment and perioperative nutrition with and without an enhanced recovery program. The goal will be to improve awareness in the surgical oncology community and at institutional level to modify current clinical practice and identify optimal treatment options.

Journal ArticleDOI
01 May 2018-Ejso
TL;DR: SMAD4 mutation is independently associated with worse outcomes among patients undergoing resection of CLM, and was an independent predictor for worse OS.
Abstract: Introduction Dorsophilia protein, mothers against decapentaplegic homolog 4 (SMAD4) is a key mediator in the transforming growth factor (TGF)-β signaling pathway and SMAD4 gene mutations are thought to play a critical role in colorectal cancer (CRC) progression. However, little is known about its influence on survival in patients undergoing resection for colorectal liver metastases (CLM). Methods Between 2005 and 2015, all patients with known SMAD4 mutation status who underwent resection of CLM were identified. Patients with SMAD4 mutation were compared to those with SMAD4 wild type. Next, the prognostic value of SMAD4 mutation was validated in a separate cohort of patients with synchronous stage IV CRC who underwent systemic therapy alone. Results Of 278 patients, 37 (13%) were SMAD4 mutant while 241 (87%) were wild type. Overall survival (OS) after hepatic resection was worse in SMAD4-mutant patients compared to SMAD4 wild type (OS rate at 3 years, 62% vs. 82%; P Conclusion SMAD4 mutation is independently associated with worse outcomes among patients undergoing resection of CLM.

Journal ArticleDOI
25 Jun 2018-Ejso
TL;DR: The available data showed no association between treatment delay and reduced overall survival in colon cancer patients, and five studies investigated the effect on disease specific survival and found no negative associations.
Abstract: Many countries have implemented cancer pathways with strict time limits dictating the pace of diagnostic testing and treatment. There are concerns that prehabilitation may worsen long-term oncological outcomes if surgery is delayed. We aimed to systematically review the literature investigating the association between increased time between diagnosis of colon cancer and surgical treatment, with special focus on survival outcomes. Methods Through a systematic search and analysis of the databases PubMed (1966–2017), EMBASE (1974–2017), CINHAL (1981–2017), and The Cochrane Library performed on June 7th, 2017, the effect of treatment delays on overall survival in colon cancer patients was reviewed. Treatment delay was defined as time from diagnosis to initiation of surgical treatment. All patients included were diagnosed with colon cancer and treated with elective curative surgery without neoadjuvant chemotherapy. This review was prospectively registered on the PROSPERO database of systematic review protocols with registration number CRD42017059774. Results Five observational studies including 13,514 patients were included. The treatment delay intervals ranged from 1 to ≥56 days. Four of the five studies found no association between time elapsed from diagnosis to surgery and reduced overall survival. One study found a clinically insignificant association between longer treatment delays and overall survival. Three studies investigated the effect on disease specific survival and found no negative associations. Conclusion The available data showed no association between treatment delay and reduced overall survival in colon cancer patients.

Journal ArticleDOI
01 Jan 2018-Ejso
TL;DR: Given the importance of effective tumor debulking, the peritoneal cancer index (PCI) may provide important information for surgical planning in patients with AOC.
Abstract: Background Effective tumor debulking is a major factor associated with a favorable prognosis in patients with advanced ovarian cancer (AOC). However, FIGO staging fails to take full account of the extent of the disease in the peritoneum, making it difficult to plan appropriate surgical treatment. In contrast, the peritoneal cancer index (PCI) can provide more detailed information about peritoneal spread. Method We evaluated the prognostic value of PCI and its association with clinicopathological features in patients with AOC. Data for 80 patients with AOC who underwent primary debulking surgery were analyzed retrospectively. PCI scores of 0–39 were calculated based on the sizes of lesions in 13 abdominopelvic regions, and patients were classified into three categories with scores of 1–10, 11–20, and >20, respectively. Clinicopathological features, including the presence of residual tumor after surgery and the incidence of postoperative complications, were assessed in relation to PCI score. Results PCI was significantly associated with suboptimal surgery and postoperative complications, as well as with preoperative CA125, ascites, prolonged surgery, FIGO stage, positive aortic lymph nodes, prolonged hospitalization, and number of visceral resections. Overall and disease-free survival was also associated with PCI, with an optimal cut-off value of 15. Multivariate analysis identified age, residual tumor, and PCI as independent prognostic factors for survival. A PCI >10 is positively associated with a poor prognosis in patients with AOC. Conclusion Given the importance of effective tumor debulking, PCI may provide important information for surgical planning in patients with AOC.

Journal ArticleDOI
11 Jan 2018-Ejso
TL;DR: High cytonuclear grade, mammographic microcalcification, young age and lack of endocrine therapy were risk factors for DCIS progression to invasive cancer.
Abstract: Background The natural history of ductal carcinoma in situ (DCIS) remains uncertain. The risk factors for the development of invasive cancer in unresected DCIS are unclear. Methods Women diagnosed with DCIS on needle biopsy after 1997 who did not undergo surgical resection for ≥1 year after diagnosis were identified by breast centres and the cancer registry and outcomes were reviewed. Results Eighty-nine women with DCIS diagnosed 1998–2010 were identified. The median age at diagnosis was 75 (range 44–94) years with median follow-up (diagnosis to death, invasive disease or last review) of 59 (12–180) months. Twenty-nine women (33%) developed invasive breast cancer after a median interval of 45 (12–144) months. 14/29 (48%) with high grade, 10/31 (32%) with intermediate grade and 3/17 (18%) with low grade DCIS developed invasive cancer after median intervals of 38, 60 and 51 months. The cumulative incidence of invasion was significantly higher in high grade DCIS than other grades (p = .0016, log-rank test). Invasion was more frequent in lesions with calcification as the predominant feature (23/50 v. 5/25; p = .042) and in younger women (p = .0002). Endocrine therapy was associated with a lower rate of invasive breast cancer (p = .048). Conclusions High cytonuclear grade, mammographic microcalcification, young age and lack of endocrine therapy were risk factors for DCIS progression to invasive cancer. Surgical excision of high grade DCIS remains the treatment of choice. Given the uncertain long-term natural history of non-high grade DCIS, the option of active surveillance of women with this condition should be offered within a clinical trial.

Journal ArticleDOI
Sung Jae Ahn1, Tae Yong Woo1, Dong Won Lee1, Dae Hyun Lew1, Seung Yong Song1 
01 Aug 2018-Ejso
TL;DR: Reconstruction methods including direct-to-implant, latissimus dorsi island flap with implant, and transverse rectus abdominis free flap showed higher rate of necrosis compared to tissue-expander reconstruction.
Abstract: Introduction Nipple-sparing mastectomy (NSM), combined with immediate breast reconstruction, has become the preferred surgical option to achieve better patient satisfaction and aesthetic outcome. However, nipple-areolar complex (NAC) ischemia and necrosis are common complications following nipple-sparing technique. Materials and methods We performed a retrospective analysis of 220 breasts that underwent NSM and immediate reconstruction from May 2010 to December 2016 at our institute. For accurate evaluation of ischemia rate after nipple-sparing mastectomy, we suggested a nipple-areolar ischemia grading system. We also found association between various factors and complications of nipple-areolar complex through statistical analysis. Results Among 220 breasts that underwent NSM in 207 patients, ischemia occurred in 141 (64.1%) breasts. However, necrosis required surgical reoperation in only 69 (31.3%) breasts. Patient factor affecting NAC complications was existence of ptosis. Also, surgical techniques for periareolar incision as well as oncologic surgeon's technique impacted NAC necrosis. Reconstruction methods including direct-to-implant, latissimus dorsi island flap with implant, and transverse rectus abdominis free flap showed higher rate of necrosis compared to tissue-expander reconstruction. Conclusion We clarified factors that affect NAC necrosis. Among them, modifiable factors were skin tension and periareolar incision. When periareolar incision is necessary, lower periareolar incision is safer than upper periareolar incision to preserve vascularity of NAC.

Journal ArticleDOI
01 May 2018-Ejso
TL;DR: To aid the development of evidence-based follow-up advise after OSCC, future research should focus on risk stratification, the value of symptom-free detection of recurrences and the active role that patients might play in determining their own following-up regimen.
Abstract: The oral cavity is the commonest subsite of head and neck squamous cell carcinoma (HNSCC). Because of the rising incidence and increasing survival, more patients will be enrolled in a routine follow-up program. This review gives an overview of the evidence and guideline recommendations concerning follow-up after oral squamous cell carcinoma (OSCC). There is limited evidence concerning the effectiveness of follow-up after OSCC. This lack of evidence is reflected in a variation in guideline recommendations with respect to test interval and duration (i.e. for 3-5 years or lifelong). Most studies on the value of routine follow-up after curative treatment include all HNSCC subsites. The available literature shows, that these subsites have a different timing of recurrence and a different risk of second primary tumors at different locations. This leaves no rationale for applying the same follow-up program to each of the HNSCC subsites. There is agreement in the literature that OSCC follow-up can either be discontinued after two or three years or should be lifelong based on the risk of second primary tumors. Many authors advocate a personalized follow-up regimen that is based on the risk of new disease rather than a one-size-fits-all surveillance program. The literature is conflicting about the survival benefits of asymptomatic detection of new disease for HNSCC. To aid the development of evidence-based follow-up advise after OSCC, future research should focus on risk stratification, the value of symptom-free detection of recurrences and the active role that patients might play in determining their own follow-up regimen.

Journal ArticleDOI
30 Aug 2018-Ejso
TL;DR: LPG with double-tract reconstruction appears superior in preventing vitamin B12 deficiency compared to LTG, particularly after 1 year after the surgery, although it offered little benefit in terms of postoperative body composition changes and QOL.
Abstract: Background This study aimed to evaluate the surgical outcomes of laparoscopic proximal gastrectomy (LPG) reconstructed by the double-tract method in comparison to those of laparoscopic total gastrectomy (LTG). Methods A retrospective review of the prospectively established database identified early gastric cancer patients who underwent LPG (n = 34) or LTG (n = 46) between January 2011 and December 2015. Baseline characteristics and surgical outcomes including postoperative complications, changes in body composition, nutritional status, and quality of life (QOL) after surgery were compared between the LPG and LTG patients. Results Operating time was significantly longer in the LTG group (240.7 ± 43.9 vs. 211.7 ± 32.8 min, p = 0.007). The incidence of grade II or more complications and the hospital stay were comparable between the groups. There was no significant difference between the groups in terms of body composition using a bioelectrical impedance method in 1 year postoperatively. Nutritional status assessed by serum hemoglobin, iron, vitamin B12, albumin, total protein, and total cholesterol levels and postoperative changes in quality of life up to 2 years after surgery were also similar between the groups. Vitamin B12 supplementation was required in 75.4% of the patients in the LTG group and 46.5% in the LPG group within 2 years after surgery (p = 0.005). Conclusion LPG with double-tract reconstruction appears superior in preventing vitamin B12 deficiency compared to LTG, particularly after 1 year after the surgery, although it offered little benefit in terms of postoperative body composition changes and QOL.

Journal ArticleDOI
01 Jul 2018-Ejso
TL;DR: Though CAA group presents worse LARS and higher faecal incontinence scores respect CRA patients, and APR is related with a worse body image, global QoL was similar in the three groups.
Abstract: Background The aim of this study was to analyze the quality of life (QoL), low anterior resection syndrome (LARS) and fecal incontinence after surgery for mid to low rectal cancer and its relationship with the type of surgical procedure performed. Methods A cross-sectional cohort survey study of 358 patients operated on for mid to low rectal cancer. Patients were included in three groups: abdominoperineal resection (APR), low mechanical colorectal anastomosis (CRA) and hand-sewn coloanal anastomosis (CAA). The QLQ-C30/CR29 questionnaires, LARS and Vaizey scores were used to study QoL and defecatory dysfunction. Multivariable analysis was used to estimate the prognostic effect of the variables on QoL and LARS scores. Results 62.6% of the patients answered the survey. The global QoL score was similar among APR, CRA and CAA. Patients' body image perception was significantly worse after APR than after CRA or CAA. LARS score was better in CRA group (p = 0.002). A major LARS was observed in 83.3% of the patients who underwent CAA and in 56.6% of the patients who underwent CRA. No relationship between surgical procedures and the global QoL score was observed. Neoadjuvant radiotherapy (p = 0.048) and CAA (p = 0.005) were associated with a major LARS. The Vaizey score was higher for CAA than for CRA (p = 0.036). Conclusions Though CAA group presents worse LARS and higher faecal incontinence scores respect CRA patients, and APR is related with a worse body image, global QoL was similar in the three groups.

Journal ArticleDOI
09 Feb 2018-Ejso
TL;DR: The present review sets a historical context before discussing recent evidence and on-going multi-centre trials in retroperitoneal sarcoma, and promising data on histologically- and molecularly-targeted chemotherapy are discussed.
Abstract: Extended surgery remains the mainstay of treatment in retroperitoneal sarcoma, although conflicting data exist on the benefit of neoadjuvant and adjuvant therapies, particularly with regard to tumour grade and histological type. Experience of radiotherapy and chemotherapy in extremity soft tissue sarcoma can inform treatment strategies, however these data cannot be universally extrapolated to the retroperitoneum where disease biology and anatomical considerations are different. The present review sets a historical context before discussing recent evidence and on-going multi-centre trials in retroperitoneal sarcoma. Promising data on histologically- and molecularly-targeted chemotherapy are discussed and the need for centralisation of retroperitoneal sarcoma services in order to facilitate large international collaborative trials is emphasised.

Journal ArticleDOI
01 Sep 2018-Ejso
TL;DR: Robot-assisted radical cystectomy and intracorporeal neobladder provides comparable oncologic outcomes of open radical cyStectomy and orthotopic neOBladder at intermediate term survival analysis.
Abstract: Aim In this study, we compared perioperative and oncologic outcomes of patients treated with either open or robot-assisted radical cystectomy and intracorporeal neobladder at a tertiary care center. Methods The institutional prospective bladder cancer database was queried for “cystectomy with curative intent” and “neobladder”. All patients underwent robot-assisted radical cystectomy and intracorporeal neobladder or open radical cystectomy and orthotopic neobladder for high-grade non-muscle invasive bladder cancer or muscle invasive bladder cancer with a follow-up length ≥2 years were included. A 1:1 propensity score matching analysis was used. Kaplan-Meier method was performed to compare oncologic outcomes of selected cohorts. Survival rates were computed at 1,2,3 and 4 years after surgery and the log rank test was applied to assess statistical significance between the matched groups. Results Overall, 363 patients (299 open and 64 robotic) were included. Open radical cystectomy patients were more frequently male (p = 0.08), with higher pT stages (p = 0.003), lower incidence of urothelial histologies (p = 0.05) and lesser adoption of neoadjuvant chemotherapy ( Conclusions Robot-assisted radical cystectomy and intracorporeal neobladder provides comparable oncologic outcomes of open radical cystectomy and orthotopic neobladder at intermediate term survival analysis.